Xarelto

Description

Rivaroxaban, a factor Xa (FXa) inhibitor, is the active ingredient in XARELTO Tablets and XARELTO for oral suspension. Its chemical name is 5-Chloro-N-({(5S)-2-oxo-3-4-(3-oxo-4-morpholinyl)phenyl-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide. The molecular formula of rivaroxaban is C19H18ClN3O5S, and it has a molecular weight of 435.89. Rivaroxaban is a pure (S)-enantiomer, presented as an odorless, non-hygroscopic, white to yellowish powder. It is only slightly soluble in organic solvents, such as acetone and polyethylene glycol 400, and is practically insoluble in water and aqueous media.

Each XARELTO tablet contains 2.5 mg, 10 mg, 15 mg, or 20 mg of rivaroxaban. The inactive ingredients in XARELTO tablets include croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. XARELTO for oral suspension is supplied as granules in bottles containing 155 mg of rivaroxaban, which provides 1 mg of rivaroxaban per mL after reconstitution. The inactive ingredients in XARELTO for oral suspension consist of anhydrous citric acid, hypromellose, mannitol, microcrystalline cellulose, carboxymethylcellulose sodium, sodium benzoate, sucralose, sweet and creamy flavor, and xanthan gum.

Uses and Indications

XARELTO is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Additionally, XARELTO is indicated for the reduction in the risk of recurrence of DVT or PE.

For patients undergoing knee or hip replacement surgery, XARELTO is indicated for the prophylaxis of DVT, which may lead to PE. It is further indicated for the prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients.

In patients with coronary artery disease (CAD), XARELTO is indicated to reduce the risk of major cardiovascular events. It is also indicated for the reduction of major thrombotic vascular events in patients with peripheral artery disease (PAD), including those who have recently undergone lower extremity revascularization due to symptomatic PAD.

XARELTO is indicated for the treatment of VTE and the reduction in the risk of recurrent VTE in pediatric patients from birth to less than 18 years of age. Furthermore, it is indicated for thromboprophylaxis in pediatric patients aged 2 years and older with congenital heart disease following the Fontan procedure.

No teratogenic or nonteratogenic effects have been mentioned.

Dosage and Administration

For the management of nonvalvular atrial fibrillation, the recommended dosage is 15 mg or 20 mg administered orally once daily with food.

In the treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), the initial dosage is 15 mg orally twice daily with food for the first 21 days. Following this period, the dosage should be adjusted to 20 mg orally once daily with food for the remainder of the treatment duration.

To reduce the risk of recurrence of DVT and/or PE in patients who remain at continued risk, a dosage of 10 mg orally once daily is recommended, which may be taken with or without food, after a minimum of 6 months of standard anticoagulant therapy.

For the prophylaxis of DVT following hip or knee replacement surgery, the recommended dosage is 10 mg orally once daily, which can be taken with or without food.

In acutely ill medical patients at risk for thromboembolic complications who are not at high risk of bleeding, the prophylactic dosage is 10 mg orally once daily, with or without food, during hospitalization and after discharge, for a total duration of 31 to 39 days.

For patients with coronary artery disease (CAD) or peripheral artery disease (PAD), the recommended dosage is 2.5 mg orally twice daily with or without food, in conjunction with aspirin at a dosage of 75–100 mg once daily.

For pediatric patients, healthcare professionals should refer to the dosing recommendations provided in the Full Prescribing Information.

Contraindications

Use of XARELTO is contraindicated in patients with active pathological bleeding due to the risk of exacerbating hemorrhagic conditions. Additionally, it is contraindicated in individuals with a severe hypersensitivity reaction to XARELTO, as this may lead to serious adverse effects.

Warnings and Precautions

XARELTO (rivaroxaban) carries significant warnings and precautions that healthcare professionals must consider to ensure patient safety.

Risk of Bleeding XARELTO is associated with a risk of serious and potentially fatal bleeding. It is imperative that healthcare providers remain vigilant for signs of hemorrhage in patients receiving this medication. An agent to reverse the anticoagulant effects of rivaroxaban is available and should be utilized in cases of severe bleeding.

Pregnancy-Related Hemorrhage Caution is advised when prescribing XARELTO to pregnant women due to the potential for obstetric hemorrhage and complications related to emergent delivery. The risks versus benefits should be carefully evaluated in this population.

Prosthetic Heart Valves The use of XARELTO is not recommended in patients with prosthetic heart valves. This contraindication is critical to prevent adverse outcomes associated with anticoagulation in this specific patient group.

Increased Risk of Thrombosis Patients with triple positive antiphospholipid syndrome are at an increased risk of thrombosis when treated with XARELTO. Therefore, its use in this population is not recommended.

Premature Discontinuation Discontinuing XARELTO prematurely can elevate the risk of thrombotic events. Healthcare providers should ensure that patients understand the importance of adherence to their prescribed regimen.

Epidural or Spinal Hematomas There have been reports of epidural or spinal hematomas in patients receiving XARELTO who are undergoing neuraxial anesthesia or spinal puncture. These hematomas can lead to long-term or permanent paralysis. It is essential to monitor patients closely for signs and symptoms of neurological impairment, and if any are observed, urgent treatment should be initiated. The benefits and risks of neuraxial interventions in patients who are or need to be anticoagulated should be carefully considered.

General Precautions Frequent monitoring for neurological impairment is recommended in patients receiving XARELTO, particularly those undergoing procedures that may increase the risk of bleeding.

No specific laboratory tests are required for the safe use of XARELTO; however, ongoing assessment of the patient's clinical status is crucial.

Side Effects

The most common adverse reaction observed in adult patients treated with XARELTO was bleeding, occurring in more than 5% of participants. In pediatric patients, the incidence of common adverse reactions was higher, with bleeding, cough, vomiting, and gastroenteritis reported in over 10% of subjects.

Serious warnings associated with XARELTO include the risk of thrombotic events following premature discontinuation of the medication. Additionally, there is a significant risk of epidural or spinal hematomas in patients receiving neuraxial anesthesia or undergoing spinal puncture, which may lead to long-term or permanent paralysis. It is crucial to monitor patients closely for signs and symptoms of neurological impairment and to provide urgent treatment if such symptoms are observed.

Clinical trial data further elucidate the safety profile of XARELTO, particularly regarding hemorrhage. In the ROCKET AF trial, the most frequent adverse reactions leading to permanent drug discontinuation were bleeding events, with incidence rates of 4.3% for XARELTO compared to 3.1% for warfarin. Major bleeding events were reported in 3.6% of patients receiving XARELTO versus 3.5% for those on warfarin. Specific types of major bleeding included intracranial hemorrhage (0.5% for XARELTO vs. 0.7% for warfarin) and gastrointestinal bleeding (2.0% for XARELTO vs. 1.2% for warfarin). Fatal bleeding occurred in 0.2% of patients on XARELTO compared to 0.5% on warfarin.

In the EINSTEIN DVT and PE studies, major bleeding events were reported in 1.0% of patients receiving XARELTO, compared to 1.7% for enoxaparin/VKA, with fatal bleeding rates of <0.1% for XARELTO versus 0.2% for enoxaparin/VKA. The EINSTEIN CHOICE study indicated a major bleeding event rate of 0.4% for XARELTO 10 mg compared to 0.3% for aspirin 100 mg, with no fatal bleeding events reported for XARELTO in this cohort. The RECORD clinical trials showed a major bleeding event rate of 0.3% for XARELTO 10 mg versus 0.2% for enoxaparin, with a fatal bleeding rate of <0.1% for XARELTO. In the MAGELLAN study, major bleeding occurred in 0.7% of patients on XARELTO 10 mg compared to 0.5% for enoxaparin, with fatal bleeding rates of <0.1% for both treatments. The COMPASS trial reported major bleeding events at an incidence rate of 2.7% for XARELTO 2.5 mg twice daily versus 1.2% for placebo.

Additional adverse reactions noted in the MAGELLAN study included cases of pulmonary hemorrhage and pulmonary hemorrhage associated with bronchiectasis. Patients with bronchiectasis or pulmonary cavitation, active cancer, dual antiplatelet therapy, or a history of active gastroduodenal ulcer or bleeding within the previous three months experienced a higher incidence of bleeding when treated with XARELTO compared to enoxaparin or placebo.

Drug Interactions

Concomitant use of strong P-glycoprotein (P-gp) inhibitors and inducers with this medication should be avoided due to potential alterations in drug metabolism and transport, which may lead to increased toxicity or reduced efficacy.

Anticoagulants are contraindicated for use alongside this medication. The combination may result in significant interactions that could compromise the safety and effectiveness of anticoagulation therapy. Monitoring of coagulation parameters is advised if anticoagulants are necessary for the patient.

Packaging & NDC

The table below lists all NDC Code configurations of Xarelto (rivaroxaban), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of XARELTO have been established in pediatric patients from birth to less than 18 years for the treatment of venous thromboembolism (VTE) and the reduction in risk of recurrent VTE. This use is supported by evidence from adequate and well-controlled studies in adults, along with additional pharmacokinetic, safety, and efficacy data from a multicenter, prospective, open-label, active-controlled randomized study involving 500 pediatric patients in the specified age range.

XARELTO has been shown to be safe and effective for pediatric patients aged 2 years and older with congenital heart disease who have undergone the Fontan procedure. This indication is further supported by data from a multicenter, prospective, open-label, active-controlled study involving 112 pediatric patients, which evaluated the pharmacokinetic properties and the safety and efficacy of XARELTO for thromboprophylaxis over 12 months in children with single ventricle physiology post-Fontan procedure.

Dosing for XARELTO in pediatric patients is available for 10 mg, 15 mg, and 20 mg tablets, with clinical studies supporting their use. However, the 2.5 mg tablets lack sufficient safety, efficacy, pharmacokinetic, and pharmacodynamic data for pediatric patients and are therefore not recommended.

It is important to note that XARELTO has not been studied in children less than 6 months who were born at less than 37 weeks of gestation, had less than 10 days of oral feeding, or weighed less than 2.6 kg; thus, dosing cannot be reliably determined or recommended in this population. While not all adverse reactions observed in adults have been reported in pediatric patients, the same warnings and precautions applicable to adults should be considered for children and adolescents.

Geriatric Use

In clinical trials involving a total of 64,943 adult patients for the approved indications of XARELTO, 64 percent were aged 65 years and older, with 27 percent being 75 years and older. The efficacy of XARELTO in geriatric patients (65 years and older) was found to be comparable to that observed in younger patients (under 65 years).

However, it is important to note that both thrombotic and bleeding event rates were higher in elderly patients. Therefore, healthcare providers should exercise caution when prescribing XARELTO to this population. Close monitoring for potential adverse events is recommended, and consideration should be given to possible dose adjustments based on individual patient factors and clinical judgment.

Pregnancy

The available data on XARELTO (rivaroxaban) in pregnant women are limited and insufficient to establish a drug-associated risk of adverse developmental outcomes. Caution is advised when prescribing XARELTO to pregnant patients due to the potential for pregnancy-related hemorrhage and/or emergent delivery. The anticoagulant effect of XARELTO cannot be reliably monitored with standard laboratory testing, necessitating careful consideration of the benefits and risks for the mother and potential risks to the fetus.

Adverse outcomes in pregnancy can occur regardless of maternal health or medication use. The estimated background risk of major birth defects and miscarriage in the U.S. general population is approximately 2–4% and 15–20%, respectively. Pregnancy itself is a recognized risk factor for venous thromboembolism, with increased risk in women with inherited or acquired thrombophilias. Pregnant women with thromboembolic disease face heightened risks of maternal complications, including pre-eclampsia, as well as increased risks for intrauterine growth restriction, placental abruption, and early and late pregnancy loss.

Given the pharmacologic activity of Factor Xa inhibitors and the potential for placental transfer, there is a risk of bleeding at any site in the fetus and/or neonate. All patients receiving anticoagulants, including pregnant women, are at risk for bleeding, which may be exacerbated during labor or delivery. The risk of bleeding must be carefully balanced against the risk of thrombotic events when considering the use of XARELTO in this population.

There are no adequate or well-controlled studies of XARELTO in pregnant women, and dosing for this population has not been established. Post-marketing experience is currently insufficient to determine a rivaroxaban-associated risk for major birth defects or miscarriage. Animal studies indicate that rivaroxaban crosses the placenta, with evidence of increased fetal toxicity, including increased resorptions, decreased number of live fetuses, and decreased fetal body weight in rabbits at doses corresponding to approximately four times the human exposure based on AUC comparisons. In rats, significant fetal body weight reductions and maternal and fetal deaths were observed at doses corresponding to about 14 times and six times the maximum human exposure, respectively.

Lactation

Rivaroxaban has been detected in human milk. However, there are insufficient data to determine the effects of rivaroxaban on breastfed infants or on milk production. In animal studies, rivaroxaban and/or its metabolites were present in the milk of lactating rats. Following a single oral administration of 3 mg/kg of radioactive ^14C-rivaroxaban to lactating rats between Day 8 to 10 postpartum, the concentration of total radioactivity was measured in milk samples collected up to 32 hours post-dose. The estimated amount of radioactivity excreted in milk within 32 hours after administration was 2.1% of the maternal dose.

The developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for rivaroxaban and any potential adverse effects on the breastfed infant from rivaroxaban or from the underlying maternal condition.

Renal Impairment

In pharmacokinetic studies, rivaroxaban exposure increased by approximately 44 to 64% in adult subjects with renal impairment compared to healthy adult subjects with normal creatinine clearance. Increases in pharmacodynamic effects were also observed.

In the ROCKET AF trial, patients with creatinine clearance (CrCl) of 30 to 50 mL/min were administered XARELTO 15 mg once daily, resulting in serum concentrations of rivaroxaban and clinical outcomes similar to those in patients with better renal function who received XARELTO 20 mg once daily. Patients with CrCl <30 mL/min were not studied; however, administration of XARELTO 15 mg once daily is expected to yield serum concentrations similar to those in patients with moderate renal impairment.

Clinical efficacy and safety studies with XARELTO did not include patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of XARELTO 15 mg once daily is anticipated to result in concentrations of rivaroxaban and pharmacodynamic activity akin to those observed in the ROCKET AF study. The implications of these concentrations for stroke reduction and bleeding risk in patients with ESRD on dialysis remain unknown.

In the EINSTEIN trials, patients with CrCl values <30 mL/min at screening were excluded. Nevertheless, administration of XARELTO is expected to produce serum concentrations similar to those in patients with moderate renal impairment (CrCl 30 to <50 mL/min). Close monitoring and prompt evaluation for signs or symptoms of blood loss are advised in patients with CrCl 15 to <30 mL/min. XARELTO should be avoided in patients with CrCl <15 mL/min.

The combined analysis of the RECORD 1–3 clinical efficacy studies did not indicate an increased bleeding risk for patients with CrCl 30 to 50 mL/min, although a possible increase in total venous thromboemboli was reported in this population. Patients with CrCl <30 mL/min at screening were excluded from these studies, but administration of XARELTO 10 mg once daily is expected to yield serum concentrations similar to those in patients with moderate renal impairment. Close monitoring for signs or symptoms of blood loss is recommended in patients with CrCl 15 to <30 mL/min, and XARELTO should be avoided in those with CrCl <15 mL/min.

Patients with CrCl values <30 mL/min were also excluded from the MAGELLAN study. In this population, a dose of XARELTO 10 mg once daily is expected to result in serum concentrations similar to those in patients with moderate renal impairment. Close monitoring for signs or symptoms of blood loss is advised in patients with CrCl 15 to <30 mL/min, and XARELTO should be avoided in patients with CrCl <15 mL/min.

Limited data are available for patients with a CrCl of 15 to 30 mL/min in the COMPASS and VOYAGER studies, where patients with CrCl <15 mL/min at screening were excluded. In patients with CrCl <30 mL/min, a dose of 2.5 mg XARELTO twice daily is expected to provide exposure similar to that in patients with moderate renal impairment, whose efficacy and safety outcomes were comparable to those with preserved renal function.

No clinical outcome data are available for the use of XARELTO with aspirin in patients with ESRD on dialysis, as these patients were not enrolled in COMPASS or VOYAGER. In patients with ESRD maintained on intermittent hemodialysis, administration of XARELTO 2.5 mg twice daily is expected to yield concentrations and pharmacodynamic activity similar to those observed in moderate renal impairment patients in the COMPASS study. The effects of these concentrations on cardiovascular risk reduction and bleeding risk in patients with ESRD on dialysis are not known.

No dosage adjustment is necessary for patients aged 1 year or older with mild renal impairment (eGFR 50 to ≤ 80 mL/min/1.73 m²). Due to limited clinical data, the use of XARELTO is not recommended in pediatric patients aged 1 year or older with moderate or severe renal impairment (eGFR <50 mL/min/1.73 m²). Additionally, there are no clinical data for pediatric patients younger than 1 year with serum creatinine results above the 97.5th percentile; therefore, the use of XARELTO is also not recommended in this population.

Hepatic Impairment

Patients with hepatic impairment may experience significant alterations in the pharmacokinetics of XARELTO. In a pharmacokinetic study, adult subjects with moderate hepatic impairment (Child-Pugh B) exhibited an increase in the area under the curve (AUC) by 127% compared to healthy adult subjects with normal liver function. Due to these findings, the use of XARELTO is contraindicated in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, as well as in those with any hepatic disease associated with coagulopathy.

Furthermore, the safety and pharmacokinetics of XARELTO have not been evaluated in patients with severe hepatic impairment (Child-Pugh C). It is important to note that there are no clinical data available regarding the use of XARELTO in pediatric patients with hepatic impairment. Therefore, careful consideration and alternative treatment options should be explored for patients with compromised liver function.

Overdosage

In the event of an overdose of XARELTO, healthcare professionals should be aware that the primary concern is the potential for hemorrhage. If bleeding complications arise, it is imperative to discontinue XARELTO and initiate appropriate therapeutic measures to manage the situation effectively.

Rivaroxaban, the active ingredient in XARELTO, exhibits limited absorption at single doses exceeding 50 mg, meaning that systemic exposure does not significantly increase beyond this threshold. In cases of overdose, the administration of activated charcoal may be considered to reduce further absorption of the drug.

It is important to note that due to rivaroxaban's high plasma protein binding, the drug is not amenable to dialysis. Therefore, alternative management strategies must be employed. Partial reversal of laboratory anticoagulation parameters can be achieved through the use of plasma products, which may assist in mitigating the effects of the overdose.

Additionally, there is an available agent specifically designed to reverse the anti-factor Xa activity of rivaroxaban. Healthcare professionals should consider this option as part of the management protocol for patients experiencing an overdose.

Nonclinical Toxicology

Rivaroxaban was evaluated for its carcinogenic potential in long-term studies involving oral gavage administration to mice and rats for a duration of up to 2 years. The results indicated that rivaroxaban did not exhibit carcinogenic properties in either species. At the highest tested dose of 60 mg/kg/day, systemic exposures (AUCs) of unbound rivaroxaban in male and female mice were found to be 1- and 2-times, respectively, the human exposure at a clinical dose of 20 mg/day. In male and female rats, systemic exposures at the same dose were 2- and 4-times, respectively, the human exposure.

In terms of mutagenicity, rivaroxaban demonstrated no mutagenic effects in bacterial assays (Ames test) and was not found to be clastogenic in V79 Chinese hamster lung cells in vitro. Additionally, results from the mouse micronucleus test in vivo confirmed the absence of mutagenic activity.

Assessment of reproductive toxicity revealed no impairment of fertility in male or female rats administered rivaroxaban at doses up to 200 mg/kg/day. This dosage resulted in exposure levels, based on the unbound AUC, that were at least 13 times greater than those observed in humans receiving a daily dose of 20 mg rivaroxaban.

Postmarketing Experience

During post-approval use of XARELTO, the following adverse reactions have been identified. These reactions were reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders include agranulocytosis and thrombocytopenia.

Hepatobiliary disorders reported are jaundice, cholestasis, and hepatitis, which encompasses hepatocellular injury.

Immune system disorders consist of hypersensitivity, anaphylactic reaction, anaphylactic shock, and angioedema.

Nervous system disorders include hemiparesis.

Renal disorders reported are anticoagulant-related nephropathy.

Respiratory, thoracic and mediastinal disorders include eosinophilic pneumonia.

Skin and subcutaneous tissue disorders consist of Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).

Injury, poisoning and procedural complications include atraumatic splenic rupture.

Patient Counseling

Healthcare providers should advise patients and/or caregivers to read the FDA-approved patient labeling, including the Medication Guide and Instructions for Use. It is essential to instruct patients to take XARELTO only as directed and to remind them not to discontinue the medication without first consulting their healthcare professional.

For patients with atrial fibrillation, it is important to advise them to take XARELTO once daily with the evening meal. Patients undergoing initial treatment for deep vein thrombosis (DVT) and/or pulmonary embolism (PE) should be instructed to take XARELTO 15 mg or 20 mg tablets with food at approximately the same time every day. For those at continued risk of recurrent DVT and/or PE after at least six months of initial treatment, advise them to take XARELTO 10 mg once daily, with or without food.

Patients who have difficulty swallowing the tablet whole should be informed that they can crush XARELTO and mix it with a small amount of applesauce, followed by food. For patients requiring a nasogastric (NG) tube or gastric feeding tube, instruct the patient or caregiver to crush the XARELTO tablet and mix it with a small amount of water before administering it via the tube.

In the event of a missed dose, healthcare providers should advise patients to follow the instructions in the Full Prescribing Information based on their specific dosing schedule. Caregivers should be instructed to administer the dose using the syringes provided in the original carton and to be aware of whether the dose needs to be taken with food. It is crucial to inform caregivers that the tablet must not be split to provide a fraction of a tablet dose.

If a child vomits or spits up the dose within 30 minutes after administration, a new dose should be given. However, if the child vomits more than 30 minutes after taking the dose, the dose should not be re-administered, and the next dose should be taken as scheduled. Caregivers should be advised to contact the child's doctor if vomiting or spitting up occurs repeatedly. For children unable to swallow whole tablets, XARELTO oral suspension may be used.

Patients should be instructed to report any unusual bleeding or bruising to their physician, as it may take longer than usual to stop bleeding, and they may bruise and/or bleed more easily while on XARELTO. If patients have had neuraxial anesthesia or spinal puncture, particularly if they are taking concomitant NSAIDs or platelet inhibitors, they should be advised to watch for signs and symptoms of spinal or epidural hematoma, such as back pain, tingling, numbness (especially in the lower limbs), muscle weakness, and stool or urine incontinence. If any of these symptoms occur, patients should contact their physician immediately.

Patients should inform their healthcare professional that they are taking XARELTO before any invasive procedure, including dental procedures. They should also be advised to inform their physicians and dentists of any prescription or over-the-counter drugs or herbal supplements they are taking or plan to take, so that potential interactions can be evaluated.

Patients must inform their physician immediately if they become pregnant or intend to become pregnant during treatment with XARELTO. Pregnant women receiving XARELTO should report any bleeding or symptoms of blood loss to their physician without delay. Additionally, patients should discuss with their physician the benefits and risks of XARELTO for both the mother and the child if they are nursing or intend to nurse during anticoagulant treatment. Those who can become pregnant should also discuss pregnancy planning with their physician.

Storage and Handling

The product is supplied in configurations that include specific NDC numbers, which should be referenced for accurate identification. It is essential to store the product at room temperature, maintaining a range between 20 °C to 25 °C (68 °F to 77 °F). Temporary excursions are permissible within the range of 15 °C to 30 °C (59 °F to 86 °F) as defined by USP Controlled Room Temperature guidelines.

It is critical to avoid freezing the granules or the reconstituted suspension to ensure product integrity. Additionally, the product must be kept out of the reach of children to ensure safety.

Additional Clinical Information

Postmarketing experience has identified several adverse events associated with the use of the medication. Clinicians should be aware of potential blood and lymphatic system disorders, including agranulocytosis and thrombocytopenia. Hepatobiliary disorders such as jaundice, cholestasis, and hepatitis (including hepatocellular injury) have also been reported.

Additionally, immune system disorders may manifest as hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, and angioedema. Neurological effects such as hemiparesis, renal complications like anticoagulant-related nephropathy, and respiratory issues including eosinophilic pneumonia have been noted. Skin reactions can include Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Lastly, there have been reports of atraumatic splenic rupture as an injury-related complication.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Xarelto as submitted by Cardinal Health 107, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)